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Objective:The underlying mechanisms for the analgesic action of paracetamol (PCT) are still under considerable debate. It has been recently proposed that PCT may act by modulating the Serotonin system. This study was conducted to verify the influence of Serotonin modulating drugs (buspirone, ondansetron, and fluoxetine) on the analgesic effect of PCT.Materials and Methods:Thirty adult albino mice were assigned to five groups: Normal saline, PCT, fluoxetine selective serotonin reuptake inhibitor (SSRI) + PCT, buspirone (5-HT1A Agonist) + PCT, and ondansetron (5HT3 antagonist) + PCT. Hot-plate and formalin test were used to determine pain threshold, tests being conducted 60 min after the last treatment. Statistical analysis was done using analysis of variance followed by Dunnet's test.Results:Coadministration of buspirone with PCT attenuated the antinociceptive activity of PCT (P < 0.001), whereas fluoxetine + PCT increased pain threshold in the hot-plate and formalin test (P = 0.0046). Analgesic effect of PCT was not affected by ondansetron in formalin models. It attenuated analgesic action of PCT in hot-plate test (P = 0.0137).Conclusion:The results suggest that 5-HT1 receptors could also be responsible for the analgesic effect of PCT. Also, higher analgesia is produced by co-administration of SSRI (fluoxetine) + PCT.

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Tuberculosis (TB) is a major cause of morbidity and mortality worldwide. India ranked fi rst amongst all TB high-burden countries, having 2.2 million incident cases and 3,00,000 deaths in 2011. 1 In order to intensify the efforts to control TB, Government of India gradually replaced National Tuberculosis Program with the Revised National Tuberculosis Control Program (RNTCP). 2 Directly observed treatment short course (DOTS) is the cornerstone of RNTCP which requires continually taking drug combinations of isoniazid (INH), rifampicin (RFP), pyrazinamide (PZA), ethambutol (EMB) and/or streptomycin (SM)every other day for 6-9 months. 3,4 Though effi cacy of DOTS is well-proven, studies have shown that utilization of multidrug regimens can cause undesirable adverse drug reactions (ADRs) of varying degrees of severity, such as hepatotoxicity, gastrointestinal disorders, allergic reactions, arthralgia, and neurological disorders. 5-9 In addition, ADRs are regarded as one of the major causes of non-adherence to anti-TB treatment. 10 ADRs may eventually contribute to the extension of treatment duration, fi nal termination, drug resistance and treatment failure. 11 As to the overall incidence of ADRs caused by anti-TB therapy, no consensus has been reached worldwide, with the incidence of ADRs ranging from 5.1% to 83.5%, respectively. 5-8,12-19 National TB programs are generally well structured to monitor patients and have a long tradition of following up care using standardized indicators, they do not collect information on ADRs directly. 20 There is a dearth of published literature about anti-TB drug-induced mortality, ABSTRACT Background: Directly observed treatment short course (DOTS) is a cornerstone of Revised National Tuberculosis Control Program of India. Adverse drug reactions (ADRs) induced by this therapy is common and it causes signifi cant morbidity and mortality. Hence, the present study was undertaken to determine the incidence and pattern of ADRs and to assess causality and severity. Methods: We conducted prospective, observational study at DOTS center of tertiary care hospital, Pune. 150 pulmonary tuberculosis patients undergoing DOTS therapy were enrolled. They were monitored weekly in an intensive phase and monthly in the continuation phase. The suspected ADRs were recorded and assessed for causality and severity by standard algorithms. Results: Incidence of ADRs due to DOTS was 19.33% & total 35 ADRs had occurred in our study. Gastrointestinal intolerance, arthralgia & itching with or without rashes were most common ADRs (incidence rates: 12.67%, 2.67% and 2.67%, respectively). On evaluation of causality by Naranjo algorithm, majority of ADRs 91.43% were "possible." As per WHO-Uppsala Monitoring Center scale, majority of ADRs 91.43% were "possible." As per Modifi ed Hartwig and Siegel scale, majority of ADRs were "moderate" (48.57%) but 8.57% were "severe." Female gender was found to be a signifi cant risk factor for developing ADRs (odds ratio: 3.08, 95% confi dence interval: 1.33-7.12. 3.33%). ADRs &...